University of Wolverhampton
Browse
Collection All
bullet
bullet
bullet
bullet
Listed communities
bullet
bullet
bullet
bullet
bullet
bullet
bullet
bullet
bullet
bullet
bullet
bullet
bullet

Wolverhampton Intellectual Repository and E-Theses > Research Institutes > Research Institute in Healthcare Science > Molecular Pharmacology Research Group > Group III metabotropic glutamate receptor activation inhibits Ca2+ influx and nitric oxide synthase activity in bone marrow stromal cells.

Please use this identifier to cite or link to this item: http://hdl.handle.net/2436/15800
    Del.icio.us     LinkedIn     Citeulike     Connotea     Facebook     Stumble it!



Title: Group III metabotropic glutamate receptor activation inhibits Ca2+ influx and nitric oxide synthase activity in bone marrow stromal cells.
Authors: Foreman, Megan A.
Gu, Yuchun
Howl, John D.
Jones, Sarah
Publicover, Stephen J.
Citation: Journal of Cellular Physiology, 204(2): 704-713
Publisher: Wiley InterScience
Issue Date: 2005
URI: http://hdl.handle.net/2436/15800
DOI: 10.1002/jcp.20353
PubMed ID: 15799084
Additional Links: http://www3.interscience.wiley.com/journal/110433685/abstract
Abstract: Nitric oxide (NO) is pivotal to bone physiology. In the central nervous system constitutive, Ca(2+)-calmodulin regulated NO synthase activity and glutamate signalling are intimately linked. Since L-glutamate signalling occurs in bone and is implicated in bone regulation, we have investigated the effect of L-glutamate on NO synthase in bone-derived cells. Treatment of marrow stromal cells with L-glutamate reduced basal NO synthase activity by 40%. Imaging showed that L-glutamate caused a rapid, usually localised and slowly-reversible fall in [Ca(2+)](i). This effect was resistant to disruption of intracellular Ca(2+) stores but sensitive to extracellular La(3+) or omission of extracellular Ca(2+), demonstrating that glutamate acts by inhibition of membrane Ca(2+) influx. The only previous description of such an effect of L-glutamate is via activation of the group III receptor, mGluR6, in the retina. Using Western blotting and RT-PCR we detected mGluR6 protein and transcripts in marrow stromal cells. The effects of L-glutamate on NOS activity and [Ca(2+)](i) in marrow stromal cells were abolished by a group III mGluR inhibitor, (S)-2-amino-2-methyl-4-phosphonobutyric acid. Recording of membrane potential showed that, similarly to the effects of retinal mGluR6 activation, L-glutamate induced membrane hyperpolarisation (-16 +/- 2 mV), which was also sensitive to group III mGluR inhibition. L-glutamate had no effect on cAMP levels. We conclude that activation of a group III mGluR in bone marrow stromal cells inhibits a Ca(2+)-permeable plasma membrane channel, reducing [Ca(2+)](i) and suppressing generation of NO. These observations directly link bone L-glutamate signalling to processes central to bone growth and regulation.
Type: Article
Language: en
Description: Metadata only
Keywords: Nitric oxide
Bone physiology
Bone marrow stromal cells
Glutamate signalling
ISSN: 0021-9541
Appears in Collections: Molecular Pharmacology Research Group

Files in This Item:

There are no files associated with this item.



Related articles on PubMed
bullet
bullet
bullet
bullet
bullet
See all 179 articles

All Items in WIRE are protected by copyright, with all rights reserved, unless otherwise indicated.

 

Fairtrade - Guarantees a better deal for Third World Producers

University of Wolverhampton, Wulfruna Street, Wolverhampton, WV1 1LY

Course enquiries: 0800 953 3222, General enquiries: 01902 321000,
Email: enquiries@wlv.ac.uk | Freedom of Information | Disclaimer and copyright | Website feedback | The University as a charity

OR Logo Powered by Open Repository | Cookies